Solid pharmaceutical or other functionally active preparations which ensure a sustained release of active ingredients over a long period of time are well known in the art. These sustained release compositions are designed to contain higher concentrations of the active ingredient than conventional, immediate release dosage forms, and they are prepared in such a manner as to effect sustained or slow release of the active ingredient into the gastrointestinal digestive tract of humans or animals over an extended period of time. Well absorbed solid oral sustained release therapeutic drug dosage forms have inherent advantages over the conventional, immediate release drugs. These delayed release forms make it possible to reduce the number of doses of the drug to be administered daily, thereby facilitating patient compliance with the treatment plan prescribed by the physician. Moreover, they ensure a constant concentration of active ingredient in the body and a more sustained drug blood level response. Moreover, by utilizing a sustained release formulation, therapeutic action is effected though less drug relative to conventional immediate release dosage forms is absorbed in the gastrointestinal tract at a given time, thereby mitigating side effects associated with a particular drug. By providing a slow and steady release of the drug over time, absorbed drug concentration spikes are mitigated or eliminated by effecting a smoother and more sustained blood level response.
Many sustained release formulations, especially those in tablet and capsule form are provided with a coating which regulates the release of active ingredient. Various coating techniques have been utilized heretofore to control the rate or the site of the release of the active ingredient in the pharmaceutical formulation.
U.S. Pat. No. 4,016,880 to Theewees, et al. describes a sustained release coating on a tablet having an osmotic solute therein. The coating has a controlled permeability to water. The drug is released through passages in the coating formed at the sites of structural weaknesses therein. The technology requires the polymers to be dissolved in organic solvents and the coating is effected by using organic solvents.
Wong, et al. in U.S. Pat. No. 4,765,989 describe an osmotic system comprising a wall comprising, in at least a part, of a semipermeable material that surrounds a compartment. The compartment contains an osmotic composition comprising a drug, e.g., nifedipine, prazosin, and doxazosin, and a second and different osmotic composition. A passageway in the wall connects the first osmotic composition with the exterior of the system. The technology requires the polymers to be dissolved in organic solvents and the coating is effected by using organic solvents.
U.S. Pat. No. 5,840,335 to Wenzel, et al. describes a system for the controlled release of an active agent wherein the system has a predetermined release rate of the active ingredient to the environment of use, and comprises (a) a shell comprised of a wall formed of a water-insoluble material which is permeable to the passage of an external fluid and (b) a core which is surrounded by said shell, the core being comprised of a water soluble active agent and a soluble polymeric adjuvant, such as polyvinyl alcohols, preferably with a residual context of 6 to 18% and an average molecular weight of 20,000 to 70,000 and a cellulose compound such as methyl cellulose, methylethylcellulose, hydroxypropylcellulose, hydroxypropylmethyl cellulose and carboxymethyl cellulose, capable of unlimited swelling. The technology requires the polymers to be dissolved in organic solvents and the coating is effected by using organic solvents.
U.S. Pat. Nos. 4,880,631 and 4,886,668 to Haslam, et al. are directed to osmotic pumps, for the controlled release of an active substance, diltiazem, L-malate to an environment of use, said pump comprising (a) a core which comprises a therapeutically effective amount of diltiazem L-malate and an effective buffering amount of sodium bitartrate surrounded by a rate controlling water insoluble wall. The coating utilizes a polymer permeable to water but impermeable to solute and a pH insensitive pore forming additive dispersed through the wall. The drug is released through the pore followed by the movement of water under an osmotic gradient across the wall. The technology requires the polymers to be dissolved in organic solvents and the coating is effected by using organic solvents.
Chen, et al. in U.S. Pat. No. 5,736,159 discloses a controlled release pharmaceutical tablet based on                (a) a compressed core which contains:                    (i) a medicament;            (ii) at least 23% to 55% by weight, based on the total weight of the core, of a water soluble osmotic agent;            (iii) a water soluble pharmaceutically acceptable polymer binder;            (iv) a water-swellable pharmaceutically acceptable polymer;            (v) a conventional pharmaceutical excipient, and                        (b) a membrane coating around the core tablet consisting essentially of:                    (i) a modified water insoluble pharmaceutically acceptable polymer; and            (ii) a pharmaceutically acceptable water soluble polymer.                        
U.S. Pat. No. 5,458,887 to Chen, et al. discloses a controlled release dosage form which comprises:
(a) an osmotic core consisting essentially of a drug and water swellable component selected from the group consisting of hydroxypropylmethyl cellulose and polyethylene oxide in admixture with the drug; and
(b) a coating comprising a water resistant polymer and a minor amount of a non-toxic water soluble pharmaceutically acceptable compound in an amount which is sufficient to dissolve in the gastrointestinal fluid and form a plurality of micropores on the outside of the tablet, the water resistant polymer being microporus to the passage of the gastrointestinal fluid. A pathway for drug release is created when the water soluble material, e.g., salt crystals, is dissolved when it comes in contact with the aqueous medium. The technology requires the polymers to be dissolved in organic solvents and the coating is effected by using organic solvents.
Baker, et al. in RE 33,994 are directed to a pharmaceutical composition for use in an aqueous environment which comprises a formulation containing a water-soluble pharmaceutically medicament, a water-insoluble, water-permeable film coating surrounding the formulation and a particulate water soluble pore-forming material dispersed within the film coating. The coating is prepared by dissolving the water insoluble film in an organic solvent and adding thereto the pore-forming material and a water modifying agent, if necessary.
U.S. Pat. No. 5,376,388 to Eichel, et al. describes a coating where the permeability is controlled by the rate of hydration of the coating. The hydratable diffusion barrier surrounds a water-soluble drug-core and comprises a film-forming polymer such as an acrylic resin or ethyl cellulose and an additive which controls the rate of hydration and permeability of the hydratable diffusion barrier selected from the group consisting of fully esterified acrylic resins containing quaternary amin side chains, lubricant anionic surfactants, plasticizers, inert water soluble materials and mixtures thereof. The rate of hydration is controlled by the selection of the polymer and various additives.
U.S. Pat. No. 4,060,598 to Groppenbächer, et al. discloses coated pharmaceutical tablets prepared by applying to a core of active material, at least one layer of a coating composition made up of a film forming aqueous synthetic resin dispersion and from 2-50% by weight of a water or alkaline soluble material and thereafter permitting the coating composition to dry. The resulting coated tablet has a core surrounded by a continuous porous matrix of synthetic resin formed from the aqueous dispersion which is insoluble in water and insoluble in the gastrointestinal tract. The pores of the continuous resin matrix are filled with a discontinuous particulate material which is water or alkaline soluble. In other words, the coating is not a continuous phase. The coated tablet initially is air and moisture tight. They describe the coating as achieving fast disintegrating or enteric disintegrating coating for tablets.
U.S. Pat. No. 5,759,577 to Barcomb discloses a compressed medicinal tablet comprising a tablet core and a sugar coating, where the sugar contains a dose of a hormonal steroid, a drug and a steroid release rate controlling amount of microcrystalline cellulose, and PVP to aid in application of the sugar coat. In Barcomb, the major portion of the coating contains the sugar, and a minor portion contains the drug, i.e., steroidal hormone, and if present, the PVP.
U.S. Pat. No. 4,248,856 to Guley, et al. describes the use of sugar coating in conjunction with a barrier coating on a core containing medicament in order to provide controlled release of pharmaceuticals. More particularly, U.S. Pat. No. 4,248,856 describes a sustained release pharmaceutical composition comprising a compressed core containing a drug, a seal coating surrounding the core and a sugar coating surrounding the seal coated core wherein,
(a) the core comprises a therapeutically effective amount of at least one drug in an amount of about 29% to about 64% by weight of the core, and the cellulose polymers hydroxypropyl methylcellulose and ethylcellulose in an amount of 30% to about 45% by weight of the core;
(b) the seal coating comprises an enteric coating material; and
(c) the sugar coating comprises sugar and a loading dose of at least one drug contained in the core in which the ratio of the drug in the sugar coating and the drug in the core is from about 1:15 to about 1:4.3.
In short, many of the technologies described in the prior art hereinabove have a common feature, a rate controlling membrane surrounding a core. In many of the aforementioned references, the membrane is made from water insoluble polymers, and various additives are added in various forms to alter the permeability of the membrane to allow and control the rate of release of drug. Most of them require the use of organic solvents. Some of them require the presence of certain ingredients, e.g., osmotic ingredients, for the formulation to function.
However, unlike the systems described hereinabove, the present invention is directed to a new and novel coating composition. In the novel coating composition of the present invention, the insoluble polymer is present in an aqueous dispersion form and the permeability as well as the strength of the membrane is adjusted by using an appropriate amount of an inert, low molecular weight water soluble ingredient which is homogeneously dispersed throughout the aqueous dispersion. As described hereinbelow, the coating composition of the present invention has several advantages over coating compositions described in the prior art or commercially used.